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Phenotypic and molecular states of IDH1 mutation-induced CD24-positive glioma stem-like cells

Mutations in IDH1 and IDH2 drive the development of gliomas. These genetic alterations promote tumor cell renewal, disrupt differentiation states, and induce stem-like properties. Understanding how this phenotypic reprogramming occurs remains an area of high interest in glioma research. Previously,...

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Main Authors: Haddock, Sara (Author) , Alban, Tyler J. (Author) , Turcan, S̨evin (Author) , Husic, Hana (Author) , Rosiek, Eric (Author) , Ma, Xiaoxiao (Author) , Wang, Yuxiang (Author) , Bale, Tejus (Author) , Desrichard, Alexis (Author) , Makarov, Vladimir (Author) , Monette, Sebastien (Author) , Wu, Wei (Author) , Gardner, Rui (Author) , Manova, Katia (Author) , Boire, Adrienne (Author) , Chan, Timothy A. (Author)
Format: Article (Journal)
Language:English
Published: June 2022
In: Neoplasia
Year: 2022, Volume: 28, Pages: 1-14
ISSN:1476-5586
DOI:10.1016/j.neo.2022.100790
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.neo.2022.100790
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S1476558622000197
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Author Notes:Sara Haddock; Tyler J. Alban; Şevin Turcan; Hana Husic; Eric Rosiek; Xiaoxiao Ma; Yuxiang Wang; Tejus Bale; Alexis Desrichard; Vladimir Makarov; Sebastien Monette; Wei Wu; Rui Gardner; Katia Manova; Adrienne Boire; Timothy A. Chan
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Summary:Mutations in IDH1 and IDH2 drive the development of gliomas. These genetic alterations promote tumor cell renewal, disrupt differentiation states, and induce stem-like properties. Understanding how this phenotypic reprogramming occurs remains an area of high interest in glioma research. Previously, we showed that IDH mutation results in the development of a CD24-positive cell population in gliomas. Here, we demonstrate that this CD24-positive population possesses striking stem-like properties at the molecular and phenotypic levels. We found that CD24 expression is associated with stem-like features in IDH-mutant tumors, a patient-derived gliomasphere model, and a neural stem cell model of IDH1-mutant glioma. In orthotopic models, CD24-positive cells display enhanced tumor initiating potency compared to CD24-negative cells. Furthermore, CD24 knockdown results in changes in cell viability, proliferation rate, and gene expression that closely resemble a CD24-negative phenotype. Our data demonstrate that induction of a CD24-positive population is one mechanism by which IDH-mutant tumors acquire stem-like properties. These findings have significant implications for our understanding of the molecular underpinnings of IDH-mutant gliomas.
Item Description:Available online 7 April 2022
Gesehen am 24.06.2022
Physical Description:Online Resource
ISSN:1476-5586
DOI:10.1016/j.neo.2022.100790

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